Circumcision bombshell

Imagine a measure that prevented 50% of new HIV infections through heterosexual intercourse, such as male circumcision has been suggested to do. Then imagine a sudden new breakthrough that required the foreskin to work.

We may be seeing this very development over the next months and years. And the key is the very same cells the circumcision proponents wish to dispose of: the Langerhans cells.

The story that follows is this in a nutshell: Langerhans cells produce a protein called Langerin. It is the primary barrier to infection and, when overcome, the Langerhans cells themselves become an entryway for infection. Normally, infection is about 1 in 100-200 incidences of vaginal intercourse. With boosted Langerin, it could be much lower. The foreskin is exceedingly rich in Langerhans cells.

This vastly complicates the conclusions of the male circumcision studies. We simply don’t know the mechanism of infection well enough to know how circumcision factors in. The bottom line may be that any new biomedical efforts to boost the presence of Langerin could be short-circuited by the removal of Langerhans cells during circumcision.

Male circumcision is a classic of act now, question later.

::edit::

Coming up in a future post is analysis of the alleged greater effectiveness of circumcision in “high risk” men, which seems to suggest this very mechanism for why men seem to resist infection better the farther away from the operation they get.

Could this be a case of the body compensating in some weird way for the loss of tissue? The question begs to be answered, Does this effect last? And of more immediate importance, Are the men giving informed consent to be the lab rats in order to find out?

Full fair use text story after the break.

MONDAY, March 5 (HealthDay News) — Researchers have discovered that cells in the mucosal lining of human genitalia produce a protein that “eats up” invading HIV — possibly keeping the spread of the AIDS virus more contained than it might otherwise be.

Even more important, enhancing the activity of this protein, called Langerin, could be a potent new way to curtail the transmission of the virus that causes AIDS, the Dutch scientists added.

Langerin is produced by Langerhans cells, which form a web-like network in skin and mucosa. This network is one of the first structures HIV confronts as it attempts to infect its host.

However, “we observed that Langerin is able to scavenge viruses from the surrounding environment, thereby preventing infection,” said lead researcher Teunis Geijtenbeek, an immunologist researcher at Vrije University Medical Center in Amsterdam.

“And since generally all tissues on the outside of our bodies have Langerhans cells, we think that the human body is equipped with an antiviral defense mechanism, destroying incoming viruses,” Geijtenbeek said.

The finding, reported in the March 4 online issue of Nature Medicine, “is very interesting and unexpected,” said Dr. Jeffrey Laurence, director of the Laboratory for AIDS Virus Research at the Weill Cornell Medical College, in New York City. “It may explain part of the relative inefficiency of HIV in being transmitted.”

Even though HIV has killed an estimated 22 million people since it was first recognized more than 25 years ago, it is actually not very good at infecting humans, relatively speaking.

For example, the human papillomavirus (HPV), which causes cervical cancer, is nearly 100 percent infectious, Laurence noted. That means that every encounter with the sexually transmitted virus will end in infection.

“On the other hand, during one episode of penile-vaginal intercourse with an HIV-infected partner, the chance that you are going to get HIV is somewhere between one in 100 and one in 200,” Laurence said.

Experts have long puzzled why HIV is relatively tough to contract, compared to other pathogens. The Dutch study, conducted in the laboratory using Langerhans cells from 13 human donors, may explain why.

When HIV comes in contact with genital mucosa, its ultimate target — the cells it seeks to hijack and destroy — are immune system T-cells. But T-cells are relatively far away (in lymph tissues), so HIV uses nearby Langerhans cells as “vehicles” to migrate to T-cells.

For decades, the common wisdom was that HIV easily enters and infects Langerhans cells. Geijtenbeek’s team has now cast doubt on that notion.

Looking closely at the interaction of HIV and Langerhans cells, they found that the cells “do not become infected by HIV-1, because the cells have the protein Langerin on their cell surface,” Geijtenbeek said. “Langerin captures HIV-1 very efficiently, and this Langerin-bound HIV-1 is taken up (a bit like eating) by the Langerhans cells and
destroyed.”

In essence, Geijtenbeek said, “Langerhans cells act more like a virus vacuum cleaner.”

Only in certain circumstances — such as when levels of invading HIV are very high, or if Langerin activity is particularly weak — are Langerhans cells overwhelmed by the virus and infected.

The finding is exciting for many reasons, not the least of which is its potential for HIV prevention, Geijtenbeek said.

“We are currently investigating whether we can enhance Langerin function by increasing the amount of Langerin on the cell surface of Langerhans cells,” he said. “This might be a real possibility, but it will take time. I am also confident that other researchers will now also start exploring this possibility.”

The discovery might also help explain differences in vulnerability to HIV infection among people.

“It is known that the Langerin gene is different in some individuals,” Geijtenbeek noted. “These differences could affect the function of Langerin. Thus, Langerhans cells with a less functional Langerin might be more susceptible to HIV-1, and these individuals are more prone to infection. We are currently investigating this.”

The finding should also impact the race to find topical microbicides that might protect women against HIV infection. Choosing compounds that allow Langerin to continue to work its magic will enhance any candidate microbicide’s effectiveness, the Dutch researcher said.

Laurence did offer one note of caution, however.

“In the test tube, this is a very important finding,” he said. “But there are many things in the test tube that don’t occur when you get into an animal or a human. Having said that, though, this is a very intriguing finding.”

Reference

Mundell, E.J. Scientists Discover ‘Datural Barrier’ to HIV. Healthday. March 5, 2007.

http://news.yahoo.com/s/hsn/20070305/hl_hsn/scientistsdiscovernaturalbarriertohiv&printer=1;_ylt=Ag3XoS9vZSbyUYdI4rIn_dq9j7AB

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